An extensive body of literature indicates that estrogen, progesterone, and testosterone play important regulatory roles in the circadian rhythms of hamsters and rats. However, this area has received little systematic attention in humans. In addition, while sleep disturbance is one of the most common complaints of peri- and post-menopausal women, little is known about the effects of the hypogonadal state, or of hormone replacement, on sleep. This experiment is designed to study the circadian rhythms and sleep of male and female volunteers under pharmacologically controlled hormonal conditions. Normal volunteers are treated with Leuprolide acetate (Lupron), a gonadotropin releasing hormone (GnRH) agonist that suppresses the endogenous secretion of gonadotropins and gonadal steroids. Hormone replacement is then prescribed, so that female subjects can be studied in three hormonal conditions (hypogonadal, estrogen, progesterone), while men are studied in two (hypogonadal, testosterone). In each hormonal condition, we study subjects circadian rhythms and sleep using sleep logs, wrist activity monitors, rectal temperature monitors, sleep EEG, and a constant routine procedure during which plasma levels of melatonin, TSH, and prolactin are measured. Ten men have completed the study, and results indicate significant decreases in prolactin levels and in the time and percent of stage 4 sleep in the hypogonadal state, compared with testosterone replacement. In addition, there are trends toward a prolonged nocturnal temperature trough, decreased REM latency, and an increase in the time and percentage of stage 3 sleep in the hypogonadal state. In men, there are no differences in the profiles of melatonin or TSH secretion between the two hormonal conditions. Eight women have completed the study, and more are being recruited, with a desired N=10. Preliminary results (N=6) show trends toward an increase in the amplitude of nocturnal melatonin secretion in the hypogonadal state; a phase advance of sleep onset and melatonin secretion in the estrogen condition; and decreased activity in the progesterone condition. - estrogen, progesterone, testosterone, circadian rhythms, sleep-wake cycle - Human Subjects